tbuckley/cabot-search huggingface dataset:
Glutaminolysis is Essential for Myofibroblast Persistence and In Vivo Targeting Reverses Fibrosis and Cardiac Dysfunction in Heart Failure
Authors: Andrew A. Gibb, Emma K. Murray, Anh T. Huynh, Ryan B. Gaspar, Tori L. Ploesch, Ken Bedi, Alyssa A. Lombardi, Pawel K. Lorkiewicz, Rajika Roy, Zolt Arany, Daniel P. Kelly, Kenneth B. Margulies, Bradford G. Hill, John W. Elrod
Journal: Circulation (2022)
Author Correction: Replicative history marks transcriptional and functional disparity in the CD8+ T cell memory pool
Authors: Kaspar Bresser, Lianne Kok, Arpit C. Swain, Lisa A. King, Laura Jacobs, Tom S. Weber, Leïla Perié, Ken R. Duffy, Rob J. de Boer, Ferenc A. Scheeren, Ton N. Schumacher
Journal: Nature Immunology (2022)
Nonalcoholic fatty liver disease and cardiovascular diseases: A Mendelian randomization study
Authors: Hexiang Peng, Siyue Wang, Mengying Wang, Ying Ye, Enci Xue, Xi Chen, Xueheng Wang, Meng Fan, Wenjing Gao, Xueying Qin, Yiqun Wu, Dafang Chen, Jin Li, Yonghua Hu, Li Wang, Tao Wu
Journal: Metabolism (2022)
When do people with abdominal symptoms need a fast track referral?
Authors: Helen Saul, Deniz Gursul, Annie Herbert, Georgios Lyratzopoulos
Journal: BMJ (2022)

The study Herbert A, Rafiq M, Pham TM, et al. Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: a cohort study. PLoS Med 2021:18;e1003708. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combining-risks-cancer-and-ibd-allows-more-fast-track-referrals/
PAR2 promotes impaired glucose uptake and insulin resistance in NAFLD through GLUT2 and Akt interference
Authors: Andrew M. Shearer, Yanling Wang, Elizabeth K. Fletcher, Rajashree Rana, Emily S. Michael, Nga Nguyen, Manal F. Abdelmalek, Lidija Covic, Athan Kuliopulos
Journal: Hepatology (2022)

Insulin resistance and poor glycemic control are key drivers of the development of NAFLD and have recently been shown to be associated with fibrosis progression in NASH. However, the underlying mechanisms involving dysfunctional glucose metabolism and relationship with NAFLD/NASH progression remain poorly understood. We set out to determine whether protease-activated receptor 2 (PAR2), a sensor of extracellular inflammatory and coagulation proteases, links NAFLD and NASH with liver glucose metabolism.Here, we demonstrate that hepatic expression of PAR2 increases in patients and mice with diabetes and NAFLD/NASH. Mechanistic studies using whole-body and liver-specific PAR2-knockout mice reveal that hepatic PAR2 plays an unexpected role in suppressing glucose internalization, glycogen storage, and insulin signaling through a bifurcating Gq -dependent mechanism. PAR2 activation downregulates the major glucose transporter of liver, GLUT2, through Gq -MAPK-FoxA3 and inhibits insulin-Akt signaling through Gq -calcium-CaMKK2 pathways. Therapeutic dosing with a liver-homing pepducin, PZ-235, blocked PAR2-Gq signaling and afforded significant improvements in glycemic indices and HbA1c levels in severely diabetic mice.This work provides evidence that PAR2 is a major regulator of liver glucose homeostasis and a potential target for the treatment of diabetes and NASH.
Global survey on COVID-19 beliefs, behaviours and norms
Authors: Avinash Collis, Kiran Garimella, Alex Moehring, M. Amin Rahimian, Stella Babalola, Nina H. Gobat, Dominick Shattuck, Jeni Stolow, Sinan Aral, Dean Eckles
Journal: Nature Human Behaviour (2022)
Structural Racism and Suicide Prevention for Ethnoracially Minoritized Youth: A Conceptual Framework and Illustration Across Systems
Authors: Kiara Alvarez, Lillian Polanco-Roman, Aaron Samuel Breslow, Sherry Molock
Journal: American Journal of Psychiatry (2022)

Suicide rates among ethnoracially minoritized youth (i.e., youth of color) peak before the age of 30, and striking disparities in access to mental health services have been identified in this age group. However, suicide prevention strategies have yet to fully address structural racism as a mechanism in producing disparities in risk, protective factors, and access to quality effective intervention for youth of color. Such an approach is critical to provide more culturally responsive mental health care. Through an adapted socio-ecological model, the authors propose the Structural Racism and Suicide Prevention Systems Framework and illustrate pathways through which structural racism impacts suicide prevention and intervention for youth of color in the United States. The authors contextualize the impact of structural racism in three key settings where youth suicide prevention occurs: mental health services, schools, and the interface between crisis care and law enforcement. The authors posit that critical attention must be paid to the intersection of mutually reinforcing, interdependent systems rather than to systems in isolation. The authors then propose recommendations to address structural racism in suicide prevention, including macro-level interventions to improve societal conditions, research strategies to inform structural solutions, training approaches to address institutional racism, and clinical approaches to address the impact of racism and racial trauma on youths and families.
Innovative Directions to Advance Mental Health Disparities Research
Authors: Crystal L. Barksdale, Eliseo Pérez-Stable, Joshua Gordon
Journal: American Journal of Psychiatry (2022)

Disparities in mental health have persisted or worsened despite our awareness of their existence, increased understanding of their causes, and efforts at reduction and mitigation. Although much is known, there is still much to be done in mental health research to meaningfully impact disparities. In November 2020, the National Institute of Mental Health (NIMH) and the National Institute of Minority Health and Health Disparities (NIMHD) co-sponsored a virtual workshop to explore the complexities of mental health disparities, which revealed several gaps and opportunities for the field to pursue to advance mental health disparities research. This article, the introduction to a Special Issue on Mental Health Disparities, provides a frame for four articles that stem from and are inspired by the virtual NIMH/NIMHD workshop, all of which illustrate innovative research on understanding the complex mechanisms of disparities and how this knowledge can be translated into effective intervention development that advances mental health equity.
Characterization and role of collagen gene expressing hepatic cells following partial hepatectomy in mice
Authors: Yusuke Kimura, Yukinori Koyama, Kojiro Taura, Aoi Kudoh, Kanae Echizen, Daichi Nakamura, Xuefeng Li, Nguyen Hai Nam, Yusuke Uemoto, Takahiro Nishio, Gen Yamamoto, Satoru Seo, Keiko Iwaisako, Akira Watanabe, Etsuro Hatano
Journal: Hepatology (2022)

Background and Aims: The mechanism underlying liver regeneration following partial hepatectomy (PH) is not fully elucidated. We aimed to characterize collagen gene expressing hepatic cells following PH and examine their contribution to liver regeneration. Approach and Results: Col‐GFP mice, which express GFP under the control of the collagen gene promoter, were used to detect collagen gene expressing cells following PH. The GFP‐expressing cells were analyzed via single‐cell RNA sequencing (scRNA‐seq). Additionally, Col‐ER Cre/RFP and Col‐ER Cre/DTA mice were utilized to examine the cell fates and functional roles of collagen gene expressing cells in liver regeneration, respectively. The number of collagen gene expressing cells was found to be increased on day 3 and subsequently decreased on day 7 following PH. ScRNA‐seq analysis of sorted collagen gene expressing cells showed that the regenerating liver was characterized by three distinct hepatic stellate cell (HSC) clusters, including one representing classic myofibroblasts. The other HSC clusters included an intermediately activated HSC cluster and a proliferating HSC cluster. Of these, the latter cluster was absent in the CCl 4 ‐induced liver fibrosis model. Cell fate tracing analysis using Col‐ER Cre/RFP mice demonstrated that the collagen gene expressing cells escaped death during regeneration and remained in an inactivated state in the liver. Further, depletion of these cells using Col‐ER Cre/DTA mice resulted in impaired liver regeneration. Conclusions: Heterogeneous HSC clusters, one of which was a unique proliferating cluster, were found to appear in the liver following PH. Collagen gene expressing cells, including HSCs, were found to promote liver regeneration.
Development and initial validation of the <scp>HS‐IGA</scp> : a novel hidradenitis suppurativa‐specific investigator global assessment for use in interventional trials*
Authors: Amit Garg, Carla Zema, Katherine Kim, Weihua Gao, Naijun Chen, Gregor B.E. Jemec, Joslyn Kirby, Linnea Thorlacius, Bente Villumsen, John R. Ingram
Journal: British Journal of Dermatology (2022)

Background Few validated instruments exist for use in hidradenitis suppurativa (HS) trials. Objectives To develop a novel HS Investigator Global Assessment (HS-IGA) and to validate its psychometric properties. Methods Development of HS-IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test–retest reliability, predictive validity, responsiveness and clinical meaningfulness. Results There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely <10 and were highest in axillary and inguinal regions. The mean and median number of regions involved were ≤ 3 for individual lesions and combinations. Regardless of lesion type, axillary and inguinal regions most influenced the HS-IGA score. Accordingly, regions were combined into a six-point IGA based on the maximum lesion number in either upper or lower body regions with a score of 0 (0–1 lesions), 1 (2–5), 2 (6–10), 3 (11–15), 4 (16–20) and 5 (≥ 20 lesions). The intraclass correlation coefficient for test–retest reliability was 0·91 (95% confidence interval 0·87–0·94). Spearman's rank order correlations (SROCs) with HS-PGA and Hidradenitis Suppurativa Clinical Response (HiSCR) were 0·73 and 0·51, respectively (P < 0·001 for both comparisons). SROCs with Dermatology Life Quality Index (DLQI), pain numerical rating scale and HS-QoL were 0·42, 0·34 and –0·25, respectively (P < 0·001 for all comparisons). HS-IGA was responsive at weeks 12 and 36. Predictive convergent validity was very good with HS-PGA (area under the curve = 0·89) and with HiSCR (area under the curve = 0·82). Predictive divergent validity was low with DLQI and HS-QoL. Conclusions HS-IGA has moderate-to-strong psychometric properties and is simple to calculate.
A self-delivery chimeric peptide for high efficient cell membrane-targeting low-temperature photothermal/photodynamic combinational therapy and metastasis suppression of tumor
Authors: Pei-Ling Chen, Pei-Ying Huang, Jiao-Yu Chen, Qun-Ying Shi, Yin-Yin Zhu, Yi Chen, Li-Han Liu, Xian-Zheng Zhang
Journal: Biomaterials (2022)
Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile
Authors: Alejandro Jara, Eduardo A. Undurraga, José R. Zubizarreta, Cecilia González, Johanna Acevedo, Alejandra Pizarro, Verónica Vergara, Mario Soto-Marchant, Rosario Gilabert, Juan Carlos Flores, Pamela Suárez, Paulina Leighton, Pablo Eguiguren, Juan Carlos Ríos, Jorge Fernandez, Heriberto García-Escorza, Rafael Araos
Journal: Nature Medicine (2022)

The outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3-5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac's inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5-39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6-75.2) against hospitalization and 69.0% (95% CI, 18.6-88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3-5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.
The Intergenerational Impact of Structural Racism and Cumulative Trauma on Depression
Authors: Sidney H. Hankerson, Nathalie Moise, Diane Wilson, Bernadine Y. Waller, Kimberly T. Arnold, Cristiane Duarte, Claudia Lugo-Candelas, Myrna M. Weissman, Milton Wainberg, Rachel Yehuda, Ruth Shim
Journal: American Journal of Psychiatry (2022)

Depression among individuals who have been racially and ethnically minoritized in the United States can be vastly different from that of non-Hispanic White Americans. For example, African American adults who have depression rate their symptoms as more severe, have a longer course of illness, and experience more depression-associated disability. The purpose of this review was to conceptualize how structural racism and cumulative trauma can be fundamental drivers of the intergenerational transmission of depression. The authors propose that understanding risk factors for depression, particularly its intergenerational reach, requires accounting for structural racism. In light of the profoundly different experiences of African Americans who experience depression (i.e., a more persistent course of illness and greater disability), it is critical to examine whether an emerging explanation for some of these differences is the intergenerational transmission of this disorder due to structural racism.
Sex and central obesity in heart failure with preserved ejection fraction
Authors: Hidemi Sorimachi, Kazunori Omote, Massar Omar, Dejana Popovic, Frederik H. Verbrugge, Yogesh N.V. Reddy, Grace Lin, Masaru Obokata, John M. Miles, Michael D. Jensen, Barry A. Borlaug
Journal: European Journal of Heart Failure (2022)
British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults
Authors: Anjan Dhar, Hasan N Haboubi, Stephen E Attwood, Marcus K H Auth, Jason M Dunn, Rami Sweis, Danielle Morris, Jenny Epstein, Marco R Novelli, Hannah Hunter, Amanda Cordell, Sharon Hall, Jamal O Hayat, Kapil Kapur, Andrew Robert Moore, Carol Read, Sarmed S Sami, Paul J Turner, Nigel J Trudgill
Journal: Gut (2022)

Background Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. Methods The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. Results Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. Conclusions These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
Reply
Authors: Antonio D'Alessio, Claudia Angela Maria Fulgenzi, David J. Pinato
Journal: Hepatology (2022)

Antonio D'Alessio received travel support and consultancy fees from Roche. David J. Pinato consults and received grants from Bristol-Myers Squibb. He consults for ViiV Healthcare, Bayer Healthcare, Roche, Eisai, and the Falk Foundation. He receives grants from MSD.
Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study
Authors: Ronald B. Goldberg, Trevor J. Orchard, Jill P. Crandall, Edward J. Boyko, Matthew Budoff, Dana Dabelea, Kishore M. Gadde, William C. Knowler, Christine G. Lee, David M. Nathan, Karol Watson, Marinella Temprosa
Journal: Circulation (2022)

Lifestyle intervention and metformin have been shown to prevent diabetes; however, their efficacy in preventing cardiovascular disease associated with the development of diabetes is unclear. We examined whether these interventions reduced the incidence of major cardiovascular events over a 21-year median follow-up of participants in the DPP trial (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study).
Multiscale design of stiffening and ROS scavenging hydrogels for the augmentation of mandibular bone regeneration
Authors: Yanlin Wu, Xuan Li, Yimin Sun, Xiujun Tan, Chenglin Wang, Zhenming Wang, Ling Ye
Journal: Bioactive Materials (2022)

Although biomimetic hydrogels play an essential role in guiding bone remodeling, reconstructing large bone defects is still a significant challenge since bioinspired gels often lack osteoconductive capacity, robust mechanical properties and suitable antioxidant ability for bone regeneration. To address these challenges, we first engineered molecular design of hydrogels (gelatin/polyethylene glycol diacrylate/2-(dimethylamino)ethyl methacrylate, GPEGD), where their mechanical properties were significantly enhanced via introducing trace amounts of additives (0.5 wt%). The novel hybrid hydrogels show high compressive strength (>700 kPa), stiff modulus (>170 kPa) and strong ROS-scavenging ability. Furthermore, to endow the GPEGD hydrogels excellent osteoinductions, novel biocompatible, antioxidant and BMP-2 loaded polydopamine/heparin nanoparticles (BPDAH) were developed for functionalization of the GPEGD gels (BPDAH-GPEGD). In vitro results indicate that the antioxidant BPDAH-GPEGD is able to deplete elevated ROS levels to protect cells viability against ROS damage. More importantly, the BPDAH-GPEGD hydrogels have good biocompatibility and promote the osteo differentiation of preosteoblasts and bone regenerations. At 4 and 8 weeks after implantation of the hydrogels in a mandibular bone defect, Micro-computed tomography and histology results show greater bone volume and enhancements in the quality and rate of bone regeneration in the BPDAH-GPEGD hydrogels. Thus, the multiscale design of stiffening and ROS scavenging hydrogels could serve as a promising material for bone regeneration applications.
Fine-mapping studies distinguish genetic risks for childhood- and adult-onset asthma in the HLA region
Authors: Selene M. Clay, Nathan Schoettler, Andrew M. Goldstein, Peter Carbonetto, Matthew Dapas, Matthew C. Altman, Mario G. Rosasco, James E. Gern, Daniel J. Jackson, Hae Kyung Im, Matthew Stephens, Dan L. Nicolae, Carole Ober
Journal: Genome Medicine (2022)

Genome-wide association studies of asthma have revealed robust associations with variation across the human leukocyte antigen (HLA) complex with independent associations in the HLA class I and class II regions for both childhood-onset asthma (COA) and adult-onset asthma (AOA). However, the specific variants and genes contributing to risk are unknown.We used Bayesian approaches to perform genetic fine-mapping for COA and AOA (n=9432 and 21,556, respectively; n=318,167 shared controls) in White British individuals from the UK Biobank and to perform expression quantitative trait locus (eQTL) fine-mapping in immune (lymphoblastoid cell lines, n=398; peripheral blood mononuclear cells, n=132) and airway (nasal epithelial cells, n=188) cells from ethnically diverse individuals. We also examined putatively causal protein coding variation from protein crystal structures and conducted replication studies in independent multi-ethnic cohorts from the UK Biobank (COA n=1686; AOA n=3666; controls n=56,063).Genetic fine-mapping revealed both shared and distinct causal variation between COA and AOA in the class I region but only distinct causal variation in the class II region. Both gene expression levels and amino acid variation contributed to risk. Our results from eQTL fine-mapping and amino acid visualization suggested that the HLA-DQA1*03:01 allele and variation associated with expression of the nonclassical HLA-DQA2 and HLA-DQB2 genes accounted entirely for the most significant association with AOA in GWAS. Our studies also suggested a potentially prominent role for HLA-C protein coding variation in the class I region in COA. We replicated putatively causal variant associations in a multi-ethnic cohort.We highlight roles for both gene expression and protein coding variation in asthma risk and identified putatively causal variation and genes in the HLA region. A convergence of genomic, transcriptional, and protein coding evidence implicates the HLA-DQA2 and HLA-DQB2 genes and HLA-DQA1*03:01 allele in AOA.
Screening for Primary Open-Angle Glaucoma
Authors: Jill Jin
Journal: JAMA (2022)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MA, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; John W. Epling Jr, MD, MSEd; Carlos Roberto Jaén, MD, PhD, MS; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; John M. Ruiz, PhD; Melissa A. Simon, MD, MPH; James Stevermer, MD, MSPH; John B. Wong, MD
Covid-19: Vaccine effectiveness wanes more rapidly for cancer patients, study finds
Authors: Jacqui Wise
Journal: BMJ (2022)

Covid-19: Vaccine effectiveness wanes more rapidly for cancer patients, study finds Jacqui WiseCovid-19 vaccination is effective for cancer patients but protection wanes much more rapidly than in the general population, a large study has found. 1 Vaccine effectiveness is much lower in people with leukaemia or lymphoma, those with a recent cancer diagnosis, and those who have had radiotherapy or systemic anti-cancer treatments within the past year, according to the research published in Lancet Oncology.